Medical Specialties Commons^™

Apathy And Brain Atrophy During The First Year Of Moderate-Severe Traumatic Brain Injury: A Longitudinal Study, Gulnaz Kudoiarova

Dissertations, Theses, and Capstone Projects

Apathy, defined as disinterest and loss of motivation, is a common complication after moderate-severe traumatic brain injury (msTBI). The existing body of research in various neurological and neurodegenerative disorders suggests that apathetic symptoms may be associated with variation in the volume of the brain regions such as dorsal anterior cingulate cortex and ventral striatum. However, the longitudinal pattern of TBI-induced atrophy in these key regions and its relationship with apathy symptoms remain to be demonstrated. The current study aimed to describe the atrophy pattern in the anterior cingulate gyrus (ACG) and the nucleus accumbens (NAc; part of ventral striatum) after …

Longitudinal Changes Of Regional Myelin Water Fraction During First Year After Moderate-To-Severe Diffuse Traumatic Brain Injury, Likowsky L. Desir

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is a worldwide health issue with a highly heterogeneous disease characterization, including widespread white matter damage in the brain. Most non-invasive white matter imaging methods currently available, including diffusion tensor imaging (DTI), cannot reliably measure the degree of neurodegeneration due to various confounds, making it challenging to select an endpoint measure for neuroprotective clinical trials. The present study investigates longitudinal white matter changes, measured by a novel imaging metric, apparent myelin water fraction (aMWF), and its relationship with neuropsychological measures during the first year after TBI. Data from 15 adult patients with moderate-to-severe TBI and 30 …

Cross-Sectional Analysis Of Baseline Visual Parameters In Subjects Recruited Into The Rescue And Reverse Nd4-Lhon Gene Therapy Studies, Mark Moster, Robert C Sergott, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Molly Scannell Bryan, Gerard Smits, Valérie Biousse, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Adam A. Debusk, Michele Carbonelli, Rabih Hage, Siegfried Priglinger, Rustum Karanjia, Laure Blouin, Magali Taiel, Barrett Katz, José Alain Sahel

Wills Eye Hospital Papers

OBJECTIVE: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

METHODS: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters …

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy For Leber Hereditary Optic Neuropathy: The Restore Study, Valérie Biousse, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Robert C Sergott, Rabih Hage, Simona Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Laure Blouin, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a …

Takayasu Arteritis: A Rare Cause Of Chronic Headache, Linda Barasa, Adil Salyani, Jillo Bika, Fred Otieno, Dilraj Sokhi

Internal Medicine, East Africa

Chronic headache can be a presenting manifestation of Takayasu arteritis, although patients usually have other characteristic features. A thorough clinical assessment remains key in the evaluation of chronic headache.

Exogenous Inter-Α Inhibitor Proteins Prevent Cell Death And Improve Ischemic Stroke Outcomes In Mice, Louise D Mccullough, Meaghan Roy-O'Reilly, Yun-Ju Lai, Anthony Patrizz, Yan Xu, Juneyoung Lee, Aleah Holmes, Daniel C Kraushaar, Anjali Chauhan, Lauren H Sansing, Barbara S Stonestreet, Liang Zhu, Julia Kofler, Yow-Pin Lim, Venugopal Reddy Venna

Faculty, Staff and Students Publications

Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading to neutralization of histone-associated cytotoxicity in models of sepsis. Many of these detrimental processes also play critical roles in the pathophysiology of ischemic stroke. In this study, we first assessed the clinical relevance of IAIPs in stroke and then tested the therapeutic efficacy of exogenous IAIPs in several experimental stroke models. IAIP levels were reduced in both ischemic stroke patients and in mice subjected to experimental ischemic stroke when …

Intra-Arterial Combination Therapy For Experimental Acute Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Amanda A. Gorman, Gregory J. Bix, Justin F. Fraser

Neurosurgery Faculty Publications

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra-arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra-arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L-type calcium channels, whereas lubeluzole, …

Total Body Photography And Sequential Digital Dermoscopy Imaging For Melanoma Surveillance In Patients Starting Natalizumab For Multiple Sclerosis, Tyler Nussinow Ba, Amanda Robinson Np, Biljana Beretich Md, Kathryn Stevens Np, Elizabeth Seiverling Md

Journal of Maine Medical Center

Introduction: Natalizumab is an integrin receptor antagonist that has been approved by the Food and Drug Administration to treat multiple sclerosis and Crohn’s disease. The drug has been linked to an increased risk of melanoma. This brief report highlights an innovative clinical approach for monitoring the skin of patients prescribed natalizumab.

Methods: We include 2 cases from our skin oncology clinic and a literature review on the incidence of melanoma in patients prescribed natalizumab between 2004 and 2019.

Results: In addition to our 2 cases, we found 193 reports of patients with melanoma who were prescribed natalizumab. We propose an …

Difficulty Breathing Or Just A Case Of The Nerves? Incidental Finding Of Primary Pleural Schwannoma In A Covid-19 Survivor, Daania Shoaib, Muhammad Nauman Zahir, Saqib R. Khan, Adnan Jabbar, Yasmin Abdul Rashid

Section of Haematology/Oncology

Schwannoma is a rare tumor that arises from the Schwann cells, which are specialized, myelin-producing cells of the peripheral nerve sheaths. As anatomic logic would dictate, these masses commonly occur in the skull base, cerebellopontine angle, and posterior spinal roots. Of this already rare entity, rarer still are the pleural schwannomas, representing approximately 1-2% of thoracic tumors. These tumors commonly affect adults with a propensity for the third and sixth decades of life and a comparative male predilection. Schwannomas are benign, indolent, and follow an asymptomatic course. As such, they often come to light incidentally.
Here we report a case …

Cognitive And Behavioral Domains That Reliably Differentiate Normal Aging And Dementia In Down Syndrome, Jordan P. Harp, Lisa M. Koehl, Kathryn L. Van Pelt, Christy L. Hom, Eric Doran, Elizabeth Head, Ira T. Lott, Frederick A. Schmitt

Neurology Faculty Publications

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer’s disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales—Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by …

Microrna-146a-5p, Neurotropic Viral Infection And Prion Disease (Prd), Aileen I. Pogue, Walter J. Lukiw

School of Graduate Studies Faculty Publications

The human brain and central nervous system (CNS) harbor a select sub-group of potentially pathogenic microRNAs (miRNAs), including a well-characterized NF-kB-sensitive Homo sapiens microRNA hsa-miRNA-146a-5p (miRNA-146a). miRNA-146a is significantly over-expressed in progressive and often lethal viral- and prion-mediated and related neurological syndromes associated with progressive inflammatory neurodegeneration. These include ~18 different viral-induced encephalopathies for which data are available, at least ~10 known prion diseases (PrD) of animals and humans, Alzheimer’s disease (AD) and other sporadic and progressive age-related neurological disorders. Despite the apparent lack of nucleic acids in prions, both DNA- and RNA-containing viruses along with prions significantly induce miRNA-146a …

Theta-Burst Stimulation Entrains Frequency-Specific Oscillatory Responses., Ethan A. Solomon, Michael R. Sperling, Ashwini D. Sharan, Paul A. Wanda, Deborah F. Levy, Anastasia Lyalenko, Isaac Pedisich, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

BACKGROUND: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.

OBJECTIVE: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations …

Advances In The Diagnosis And Treatment Of Krabbe Disease, David A Wenger, Paola Luzi, Mohammad Rafi

Department of Neurology Faculty Papers

Krabbe disease is an autosomal recessive leukodystrophy caused by pathogenic variants in the galactocerebrosidase (GALC) gene. GALC activity is needed for the lysosomal hydrolysis of galactosylceramide, an important component of myelin. While most patients are infants, older patients are also diagnosed. Starting in 1970, a diagnosis could be made by measuring GALC activity in leukocytes and cultured cells. After the purification of GALC in 1993, the cDNA and genes were cloned. Over 260 disease-causing variants as well as activity lowering benign variants have been identified. While some pathogenic variants can be considered “severe,” others can be considered “mild.” The combination …

Analysis Of Deep Brain Stimulation Lead Targeting In The Stimulation Of Anterior Nucleus Of The Thalamus For Epilepsy Clinical Trial., Robert E. Gross, Robert S. Fisher, Michael R. Sperling, Jonathon E. Giftakis, Paul H. Stypulkowski

Department of Neurology Faculty Papers

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an effective therapy for patients with drug-resistant focal epilepsy. Best practices for surgical targeting of the ANT can be refined as new information becomes available regarding effective stimulation sites.

OBJECTIVE: To conduct a retrospective analysis of the relationship between outcomes (seizure reduction during year 1) and DBS lead locations in subjects from the SANTÉ pivotal trial (Stimulation of ANT for Epilepsy) based upon recent clinical findings.

METHODS: Postoperative images from SANTÉ subjects (n = 101) were evaluated with respect to lead trajectory relative to defined anatomic …

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …

Psychological Problems Among Patients With Chronic Medical Disorders During The Covid-19 Pandemic, Ali Akbar Asadi-Pooya, Seyed Ali Nabavizadeh, Saeid Sadeghian, Mina Shahisavandi, Zohreh Barzegar, Abdullah Nezafat, Nahid Ashjazadeh, Hamed Bazrafshan Drissi, Ali Sahraian

Department of Neurology Faculty Papers

The aim of the current study was to investigate the rates of stress, anxiety, and depression among people in south Iran (a group from the general population without a history of any chronic medical problems, and cohorts of patients were recruited from epilepsy, diabetes, and cardiac disease clinics). We surveyed a sample of people during September 2020: a group of the general population without a history of any chronic medical problems, people with epilepsy, people with diabetes mellitus (DM), and people with cardiac problems. The survey included four general questions and two COVID-19 specific questions [contracting COVID-19, relatives with COVID-19]. …

Promoting Partner-Inflicted Brain Injury Awareness Within The Domestic Violence Community, Christina Debowski, Heather Javaherian, Karen Park

Summer 2021 Virtual OTD Capstone Symposium

Background: Brain injury has been shown in research to decrease individuals’ ability to participate in their meaningful activities by negatively impacting their cognitive, emotional, and physical systems. Recent research has begun to indicate that survivors of domestic violence (DV) are at extreme risk for experiencing partner inflicted brain injury (PIBI)--brain injury that results from the physical violence of a survivor's intimate partner. However, despite the prevalence of PIBI within the DV community, research shows that survivors and DV service providers alike are not aware of how PIBI can impact survivors' daily life and wellbeing.

Purpose: The purpose of this project …

The Role Of Occupational Therapy With People Living With Epilepsy: A Scoping Review, Paige Peeples, Steven M. Gerardi

Summer 2021 Virtual OTD Capstone Symposium

Objective: The aim of this scoping review is to systematically examine and organize current literature describing the current roles of occupational therapists with people living with epilepsy, including assessments, interventions, and other behaviors. This will help identify current gaps in the literature to facilitate future research.

Methods: Using scoping review methodology, an electronic database search was conducted using the search terms “occupational therapy and epilepsy”. Data was extracted and charted independently by the investigator by way of finding themes and codes through analysis.

Results: The total number of studies included was 12. The primary methodology noted were case studies. …

An Occupational Therapy Practice Guide For Sport-Related Concussion In Student Athletes, Jenny Park, Steven M. Gerardi, Mary Ann Smith

Summer 2021 Virtual OTD Capstone Symposium

Sport-related concussion (SRC) is a prevalent injury that affects millions of youth and young adults every year (McKeithan et al., 2019). The sequelae associated with an SRC can interfere with a student athletes’ ability to participate in school, return to play, and perform daily tasks (DeMatteo et al., 2018). Common practice in concussion management highlights the significance of getting individuals back to engaging in all areas of their lives; and this is consistent with the emphasis on participation by occupational therapy (OT) practitioners (DeMatteo et al., 2018). Despite the beneficial role that OT may offer, not only is there limited …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Research

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Macrocyclic Immunoproteasome Inhibitors As A Potential Therapy For Alzheimer's Disease, Min Jae Lee, Deepak Bhattarai, Hyeryung Jang, Ahreum Baek, In Jun Yeo, Seongsoo Lee, Zachary Miller, Sukyeong Lee, Jin Tae Hong, Dong-Eun Kim, Wooin Lee, Kyung Bo Kim

Faculty, Staff and Students Publications

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 (

Pulmonary Function Decline In Amyotrophic Lateral Sclerosis, Terry D. Heiman-Patterson, Ossama Khazaal, Daohai Yu, Michael E. Sherman, Edward J. Kasarskis, Carlayne E. Jackson, Peg Niv Study Group

Neurology Faculty Publications

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each …

Hur Plays A Positive Role To Strengthen The Signaling Pathways Of Cd4+T Cell Activation And Th17 Cell Differentiation, Shiguang Yu, Morgan Tripod, Ulus Atasoy, Jing Chen

Department of Neurology Faculty Papers

After antigen and/or different cytokine stimulation, CD4⁺ T cells activated and differentiated into distinct T helper (Th) cells via differential T cell signaling pathways. Transcriptional regulation of the activation and differentiation of naïve CD4⁺ T cells into distinct lineage Th cells such as Th17 cells has been fully studied. However, the role of RNA-binding protein HuR in the signaling pathways of their activation and differentiation has not been well characterized. Here, we used HuR conditional knockout (HuR KO) CD4⁺ T cells to study mechanisms underlying HuR regulation of T cell activation and differentiation through distinct signaling pathways. …

Pathophysiology Of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review., William S. Dodd, Dimitri Laurent, Aaron S. Dumont, David M. Hasan, Pascal M. Jabbour, Robert M. Starke, Koji Hosaka, Adam J. Polifka, Brian L. Hoh, Nohra Chalouhi

Department of Neurosurgery Faculty Papers

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have …

Rsv-Induced Guillain–Barré Syndrome, Priyanga Jayakumar, Christe Shen, Dylan Goldsmith, Steven Lippmann

The University of Louisville Journal of Respiratory Infections

A patient with respiratory syncytial virus-induced Guillain–Barré Syndrome and acute disseminated encephalomyelitis is presented. This virus is the most common cause of upper respiratory infections, and it can become an etiology for extra-pulmonary pathology with serious complications. Such a case is rare, but the possibility of adverse comorbidities makes early diagnosis and treatment important.

Treatment Of Thoracolumbar Type A3 Fractures Using A Percutaneous Intravertebral Expandable Titanium Implant: Long-Term Follow-Up Results Of A Pilot Single Center Study., David C Noriega, Jesus Crespo-Sanjuan, Wayne J. Olan, Ruben Hernandez-Ramajo, Douglas P Bell, J Javier Castrodeza Sanz, Gregorio De Jesus Labrador Hernandez, Israel Sanchez-Lite, Francisco Ardura

Neurological Surgery Faculty Publications

BACKGROUND: There are controversies about the optimal management of AO subtype A3 burst fractures. The most common surgical treatment consists of posterior fixation with pedicle screw and rod augmentation. Nevertheless, a loss of correction in height restoration and kyphotic reduction has been observed.

OBJECTIVES: The aim of this study was to assess long-term outcomes of a minimally invasive technique using a percutaneous intravertebral expandable titanium implant (PIETI).

STUDY DESIGN: This prospective, single center, pilot study was carried out on a consecutive case series of 44 patients with acute (< 2 weeks) traumatic thoracolumbar fractures AO type A3. The average follow-up was 5.6 years.

SETTING: A single center in Castilla y Leon, SpainMETHODS: Clinical outcomes …

In Adults Suffering Acute Large Cerebral Vessel Occlusion, Is Direct Mechanical Thrombectomy More Effective Than Treatment With Tpa For Reducing Long-Term Morbidity?, Collin Barry

Theses and Graduate Projects

Background: Discussion whether intravenous tPA or mechanical thrombectomy is the ideal choice for treatment of acute ischemic strokes has been debated around the medical community for last three decades. However still, after several clinical trials, it is still unclear if one is superior to the other.

Methods: This meta-analysis pooled several different results from studies revolving around treatment of acute ischemic stroke. The goal of this paper was to evaluate whether previous clinical trials favoring mechanical thrombectomy had sufficient research to prove it is superior to treatment with tPA in reducing long-term morbidity. Primary outcomes measured were the modified Rankin …

Solitary Langerhans Cell Histiocytosis Of Skull: Case Report With One-Year Follow-Up, Muhammad Junaid, Syed Sarmad Bukhari, Ali Afzal

Section of Neurosurgery

Langerhans cell histiocytosis (LCH) is a rare disorder characterised by increased production of Langerhans-type histiocytes. It is more common in the pediatric age group with a predilection for osseous involvement, though any organ may be involved. A 10-year male child was brought to the neurosurgical clinic with a slow growing painful tender mass on the head. Initial attempt to biopsy the lesion failed due to excessive bleeding. It was later imaged and removed with a frontal craniotomy. Histopathological evaluation along with immunohistochemistry revealed the true nature of the lesion. Follow-up revealed complete excision of the lesion and no recurrence at …

Seizure Control After Surgical Resection Of Insular Glioma, Fatima Gauhar, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Medical College Documents

Insular gliomas most commonly present with drug-resistant seizures, irrespective of the tumour grade. Even though surgery is the mainstay of treatment, complex anatomical location and close proximity to eloquent cortex makes surgical resection difficult. Herein the authors have reviewed the literature with regards to seizure control after surgical management of these tumours. The review does not address quality of life, or survival benefits of surgery. In summary, excision of these gliomas significantly improves seizure control, and extent of resection along-with trans-cortical approach are important predictors of seizure outcome.

A Phase 1b/2a Study Of Soticlestat As Adjunctive Therapy In Participants With Developmental And/Or Epileptic Encephalopathies., Jonathan J. Halford, Michael R. Sperling, Dimitrios Arkilo, Mahnaz Asgharnejad, Celia Zinger, Rengyi Xu, Matthew During, Jacqueline A. French

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

METHODS: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) . In Part A, patients with DEE and at least one bilateral motor seizure during the 4-week prospective baseline period were randomized 4:1 to receive soticlestat or placebo, in addition to their usual antiseizure medication. In Part B, all patients received open-label soticlestat. Soticlestat doses were titrated according to tolerability to a maximum of …